Alberto Montero, M.D.
Assistant Professor of Medicine
Description of Research
Dr. Montero's primary research interests focus on the development of effective immunotherapeutic strategies for the treatment of solid tumors (in particular in breast cancer and gastrointestinal malignancies). Thus far, immunotherapy has been largely an unrealized promise in the treatment of human solid tumors. Sporadic tumor regression and measurable immune response against tumor-associated antigens suggest that immunotherapy is certainly active. The ability of cytotoxic T-lymphocyte antigen 4 (CTLA4) blockade with monoclonal antibodies to induce long-term regression in a small percentage of solid tumor patients by enhancing endogenous anti-tumor immune responses is also proof of the principle that immune-based strategies work in treating solid tumors. Humans are capable of mounting immune responses against cancer antigens. However, one of the biggest obstacles in the clinical development of immune-based therapies as a viable strategy in treating solid tumors is our inability to predict in which patients immune-based therapies will be effective. The fact that only a very small percentage of solid tumor patients enrolled in immunotherapy trials derive long-term tumor regression underscores the importance of developing predictive immunologic biomarkers. Dr. Montero has a special interest in understanding how tumor derived factors lead to the accumulation of myeloid derived suppressor cells (MDSC) and what bearing circulating MDSCs have on regulatory T-cells, prognosis, and on effectiveness of cancer vaccines or other immunotherapeutic strategies. Dr. Montero's ongoing research also includes a novel glutathione mimetic (NOV-002) which is part of an investigator initiated phase II neoadjuvant trial at the University of Miami, which thus far in 17 patients with HER-2 unamplified breast cancer has shown to have an approximate 40% near pathologic and complete response rate (pCR) when combined with standard anthracycline-taxane based chemotherapy. In comparison to previously published trials, expected breast and node pCR rates for a similar chemotherapy regimen in HER-2 negative patients would be approximately 10-20%. The glutathione mimetic NOV-002 has been clinically shown to enhance the anti-tumor effect of chemotherapy, however the specific mechanisms remain unclear. Even modest increases in the cellular cysteine supply are known to elevate the intracellular glutathione levels, thereby potentiating immunological functions of lymphocytes. Clinical trials have shown that NOV-002, in combination with various chemotherapeutic agents, doubles response rates, and at the same time is associated with significant increases in circulating CD3+ T-lymphocytes, CD4+, CD8+ lymphocytes, and NK-T lymphocytes. Recent work in Dr. Montero’s laboratory has shown that NOV-002 was associated with significantly higher circulating CD8+ and CD3+ T cells in breast cancer patients with pathologic complete responses. His laboratory has also shown that (i) NOV-002 can reverse the suppressive effect of myeloid suppressor cells (MDSC) on T cells and (ii) potentiate the effect of adoptive immunotherapy in vivo.
Selected Cancer-Related Publications
- Salem ML, Diaz-Montero CM, Al-Khami AA, El-Naggar SA, Naga O, Montero AJ, Khafagy A, Cole DJ. Recovery from cyclophosphamide-induced lymphopenia results in expansion of immature dendritic cells which can mediate enhanced prime-boost vaccination antitumor responses in vivo when stimulated with the TLR3 agonist poly(I:C). J Immunol 182:2030-40, 2009. Read more »
- Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ. Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58(1):49-59, 2009. Read more »
- Montero AJ, Diaz-Montero CM, Millikan RE, Liu J, Do KA, Hodges S, Jonasch E, McIntyre BW, Hwu P, Tannir N. Cytokines and angiogenic factors in patients with metastatic renal cell carcinoma treated with interferon-alpha: association of pretreatment serum levels with survival. Ann Oncol 20:1682-7,2009. Read more »
Collaborating in the Multidisciplinary Research Program(s):